Expansion of CD1d-restricted NKT cells in patients with primary HIV-1 infection treated with interleukin-2

Moll, Markus; Snyder‐Cappione, Jennifer; Spotts, Gerald; Hecht, Frederick M.; Sandberg, Johan K.; Nixon, Douglas F.

doi:10.1182/blood-2005-09-3636

Cited by 51 publications

(41 citation statements)

References 20 publications

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“…During chronic HIV-1 infection, iNKT cells show persistent severe functional impairment and elevated PD-1 expression [23]. Note that antiretroviral therapy only enhances the frequency of circulating iNKT cells when IL-2 is co-administered [24]. Both invariant and non-invariant subsets of NKT cells are present at relatively high frequencies in the mouse liver and at somewhat lower frequencies in human liver.…”

Section: Changes In Human Inkt Cells During Viral Infectionsmentioning

confidence: 96%

NKT cells: Friend or foe during viral infections?

Diana

Lehuen

2009

Eur J Immunol

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NKT cells are innate-like T lymphocytes that are found in rodents and primates. They are non-conventional T cells restricted by the CD1d molecule that presents self and exogenous glycolipids. NKT cells are unique in their ability to promptly secrete copious amounts of cytokines such as IFN-c and IL-4. Once activated, NKT cells can provide maturation signals to downstream cells, including DC, NK cells, and lymphocytes, thereby contributing to both innate and acquired immunity. Accordingly, NKT cells can influence a wide array of immune responses, including tumor surveillance, maintenance of self-tolerance and anti-infectious defenses. Studies performed with NKT-cell-deficient mice have shown that these cells are critical for the clearance of various pathogens. During bacterial infections, NKT cells can be activated either indirectly by DC or directly by bacterial lipid antigens presented by CD1d. Although viruses do not contain lipid antigens, NKT cells have also been implicated in antiviral responses. The capacity of NKT cells to regulate viral immune-surveillance, either constitutively or post-activation, makes them an attractive clinical target. In this review, we summarize recent publications dealing with the functions and relevance of NKT cells in the context of viral infections, both in murine models and in humans. (Table 1). Immune evasion by impairing CD1d-mediated antigen presentationSeveral viruses have developed immune-evasion strategies that impair CD1d-mediated antigen presentation, suggesting a role for NKT cells in antiviral responses. Infection by Kaposi sarcomaassociated herpes virus down-regulates cell-surface CD1d expression [6]. This effect is due to two viral modulators of immune recognition proteins, which ubiquitinate the cytoplasmic tail of CD1d and thereby accelerates CD1d endocytosis. HSV type 1 (HSV-1) infection leads to defective CD1d recycling from the endosome to the cell surface, due to its trapping in the late endosomal compartment and resulting in reduced cell-surface expression [7]. Likewise, HIV type 1 (HIV-1) down-regulates CD1d expression by increasing CD1d internalization from the cell [50,56,[57][58][59][60] Eur. Mini-Review

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Section: Changes In Human Inkt Cells During Viral Infectionsmentioning

confidence: 96%

NKT cells: Friend or foe during viral infections?

Diana

Lehuen

2009

Eur J Immunol

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“…After a year's treatment, one can possibly see a weak, statistically insignificant [40] or significant [42] increase of NKT levels and improved cell function [41], although overall they remained depressed. This stage of recovery is apparently caused by the gradual expansion of newly produced cells of both subsets.…”

Section: Effects Of Antiretroviral Therapy On Circulating Nkt Cellsmentioning

confidence: 98%

“…Studies on the dynamics of CD4+ T cell recovery have established that HAART results in a rapid first phase increase in memory and activated T cells in the blood that is mainly due to the release of the previously lymphoid tissue-sequestered lymphocytes, followed by a second prolonged phase characterised by the continuous slow repopulation with newly produced naïve T cells [36][37][38][39]. The effects of HAART on circulating NKT cells, however, has not drawn too much attention until recently, when several studies were published in the past two years discussing the dynamics of NKT cell recovery under HAART treatment [33,[40][41][42]. Certain discrepancies exist among them, apparently owing to the differences in disease stages and treatment regimes of the cohorts, and also due to the fact that NKT cells are such a small and variable population to study.…”

Section: Effects Of Antiretroviral Therapy On Circulating Nkt Cellsmentioning

confidence: 99%

“…After the fast phase recovery, HAART treatment can maintain NKT level and prevent their further depletion [40][41][42]. After a year's treatment, one can possibly see a weak, statistically insignificant [40] or significant [42] increase of NKT levels and improved cell function [41], although overall they remained depressed.…”

Section: Effects Of Antiretroviral Therapy On Circulating Nkt Cellsmentioning

confidence: 99%

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NKT cells in HIV-1 infection

2008

Cell Res

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“…Patients with deficiencies in NKT cell development are hypersensitive to herpesvirus infection (59). There is a selective loss of circulating NKT cells during HIV-1 infection (68), and current treatments of HIV-1 patients by interleukin-2 (IL-2) or highly active antiretroviral therapy rapidly restore iNKT cell populations (49,67). In animal models, NKT-cell-deficient mice are much more susceptible to infection by herpes simplex virus type 1 (HSV-1) (21), influenza viruses (13), respiratory syncytial virus (34), and encephalomyocarditis virus (EMCV) (30).…”

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confidence: 99%

Herpes Simplex Virus 1 Glycoprotein B and US3 Collaborate To Inhibit CD1d Antigen Presentation and NKT Cell Function

Rao

Pham

Kulkarni

et al. 2011

J Virol

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Herpes simplex viruses (HSVs) are prevalent human pathogens that establish latency in human neuronal cells and efficiently evade the immune system. It has been a major medical challenge to eradicate them and, despite intensive efforts, an effective vaccine is not available. We previously showed that upon infection of antigen-presenting cells, HSV type 1 (HSV-1) rapidly and efficiently downregulates the major histocompatibility complex class I-like antigen-presenting molecule, CD1d, and potently inhibits its recognition by CD1d-restricted natural killer T (NKT) cells. It suppresses CD1d expression primarily by inhibiting its recycling to the cell surface after endocytosis. We identify here the viral glycoprotein B (gB) as the predominant CD1d-interacting protein. gB initiates the interaction with CD1d in the endoplasmic reticulum and stably associates with it throughout CD1d trafficking. However, an additional HSV-1 component, the serine-threonine kinase US3, is required for optimal CD1d downregulation. US3 expression in infected cells leads to gB enrichment in the trans-Golgi network (TGN) and enhances the relocalization of both gB and CD1d to this compartment, suggesting that following internalization CD1d is translocated from the endocytic pathway to the TGN by its association with gB. Importantly, both US3 and gB are required for efficient inhibition of CD1d antigen presentation and NKT cell activation. In summary, our results suggest that HSV-1 uses gB and US3 to rapidly inhibit NKT cell function in the initial antiviral response.

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Expansion of CD1d-restricted NKT cells in patients with primary HIV-1 infection treated with interleukin-2

Cited by 51 publications

References 20 publications

NKT cells: Friend or foe during viral infections?

NKT cells: Friend or foe during viral infections?

NKT cells in HIV-1 infection

Herpes Simplex Virus 1 Glycoprotein B and US3 Collaborate To Inhibit CD1d Antigen Presentation and NKT Cell Function

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